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The presence of parkinsonism features in primary progressive aphasia (PPA) is a subject of ongoing research. These features are usually more pronounced in the advanced stages of the disease, particularly in the non-fluent/agrammatic subtype, and are exceptionally rare in the logopenic variant (lvPPA). Here we report a case of a 63-year-old man presenting as language impairment, predominantly naming and word-finding difficulties, emerged alongside a left-sided internal tremor. Neurological examination revealed bilateral, left-side predominant rigidity, bradykinesia, and resting tremor. Notably, anosmia and constipation were present. Language assessments showed preserved single-word comprehension, object knowledge, and a minimal apraxia of speech, as well as sentence repetition issues. Neuroimaging and biomarker analysis supported a diagnosis of primary progressive logopenic aphasia with amyloid pathology co-existing with prominent and early parkinsonism. This case underlines the intricate relationship between language disorders, parkinsonism, and amyloid pathology in lvPPA.

IMPORTANCE: Mechanisms contributing to disability accumulation in multiple sclerosis (MS) are poorly understood. Blood neurofilament light chain (NfL) level, a marker of neuroaxonal injury, correlates robustly with disease activity in people with MS (MS); however, data on the association between NfL level and disability accumulation have been conflicting. OBJECTIVE: To determine whether and when NfL levels are elevated in the context of confirmed disability worsening (CDW). DESIGN, SETTING, AND PARTICIPANTS: This study included 2 observational cohorts: results from the Expression, Proteomics, Imaging, Clinical (EPIC) study at the University of California San Francisco (since 2004) were confirmed in the Swiss Multiple Sclerosis Cohort (SMSC), a multicenter study in 8 centers since 2012. Data were extracted from EPIC in April 2022 (sampling July 1, 2004, to December 20, 2016) and SMSC in December 2022 (sampling June 6, 2012, to September 2, 2021). The study included 2 observational cohorts in tertiary MS centers. All participants of both cohorts with available NfL results were included in the study, and no eligible participants were excluded or declined to participate. EXPOSURE: Association between NfL z scores and CDW. MAIN OUTCOME MEASURES: CDW was defined as Expanded Disability Status Scale (EDSS) worsening that was confirmed after 6 or more months and classified into CDW associated with clinical relapses (CDW-R) or independent of clinical relapses (CDW-NR). Visits were classified in relation to the disability worsening events into CDW(−2) for 2 visits preceding event, CDW(−1) for directly preceding event, CDW(event) for first diagnosis of EDSS increase, and the confirmation visit. Mixed linear and Cox regression models were used to evaluate NfL dynamics and to assess the association of NfL with future CDW, respectively. RESULTS: A total of 3906 EPIC visits (609 participants; median [IQR] age, 42.0 [35.0-50.0] years; 424 female [69.6%]) and 8901 SMSC visits (1290 participants; median [IQR] age, 41.2 [32.5-49.9] years; 850 female [65.9%]) were included. In CDW-R (EPIC, 36 events; SMSC, 93 events), NfL z scores were 0.71 (95% CI, 0.35-1.07; P < .001) units higher at CDW-R(−1) in EPIC and 0.32 (95% CI, 0.14-0.49; P < .001) in SMSC compared with stable MS samples. NfL elevation could be detected preceding CDW-NR (EPIC, 191 events; SMSC, 342 events) at CDW-NR(−2) (EPIC: 0.23; 95% CI, 0.01-0.45; P = .04; SMSC: 0.28; 95% CI, 0.18-0.37; P < .001) and at CDW-NR(−1) (EPIC: 0.27; 95% CI, 0.11-0.44; P < .001; SMSC: 0.09; 95% CI, 0-0.18; P = .06). Those findings were replicated in the subgroup with relapsing-remitting MS. Time-to-event analysis confirmed the association between NfL levels and future CDW-R within approximately 1 year and CDW-NR (in approximately 1-2 years). CONCLUSIONS AND RELEVANCE: This cohort study documents the occurrence of NfL elevation in advance of clinical worsening and may hint to a potential window of ongoing dynamic central nervous system pathology that precedes the diagnosis of CDW.

Introduction: There is limited real-world evidence on the burden of migraine among patients with prior preventive treatment failure (PPTF). In the BECOME Swiss subanalysis, we aimed to assess current prevalence of PPTF in patients with migraine seen at specialised headache centres in Switzerland and burden of migraine in these patients. Furthermore, we assessed this burden in subgroups stratified by monthly migraine days (MMDs) and number of PPTFs. Methods: BECOME was a prospective, multicentre, non-interventional two-part study conducted in 17 countries across Europe and Israel. This subanalysis includes patients visiting ten headache specialist centres in Switzerland. In part 1, patients visiting the centres over 3 months were screened by physicians for frequency of PPTF, MMD and other migraine characteristics. Patients with ≥ 1 PPTF and ≥ 4 MMDs were invited to take part in part 2. The primary endpoint was the proportion of patients with ≥ 1 PPTF (part 1). Other endpoints included proportion of patients specified by number of PPTF and MMD (part 1, part 2), and impact of migraine on patient-reported outcomes (PROs; part 2). Results: Patients (1677) from ten Swiss centres were included in part 1, of which 855 (51.0%) reported ≥ 1 PPTF. One hundred fifty-five patients were included in part 2: 6.5% reported ≥ 4 PPTFs and 43.2% reported ≥ 15 MMDs. Mean EuroQoL 5 and EuroQoL visual analogue scale (EQ-VAS) were 0.8 ± 0.2 and 69.6 ± 20.2, respectively, suggesting a mild level of impairment in the daily functioning and self-reported health of the patients. Mean six-item Headache Impact Test (HIT-6) and modified Migraine Disability Assessment (mMIDAS) scores were 63.3 ± 6.5 and 22.7 ± 21.8, respectively, corresponding to severe migraine burden. Patients also reported impairment in work-related productivity and general activities (48.6 ± 22.8) but no associations of anxiety (7.2 ± 4.4) or depression (6.0 ± 4.4) with migraine were noted. Burden of migraine increased with increasing frequency of PPTF and MMD. Conclusions: Migraine-related quality of life, as well as work productivity are significantly affected in Swiss patients with migraine. Increasing migraine burden is associated with increasing migraine frequency and prior treatment failures.

IMPORTANCE: Diagnostic incidence data for syndromes associated with frontotemporal lobar degeneration (FTLD) in multinational studies are urgent in light of upcoming therapeutic approaches. OBJECTIVE: To assess the incidence of FTLD across Europe. DESIGN, SETTING, AND PARTICIPANTS: The Frontotemporal Dementia Incidence European Research Study (FRONTIERS) was a retrospective cohort study conducted from June 1, 2018, to May 31, 2019, using a population-based registry from 13 tertiary FTLD research clinics from the UK, the Netherlands, Finland, Sweden, Spain, Bulgaria, Serbia, Germany, and Italy and including all new FTLD-associated cases during the study period, with a combined catchment population of 11 023 643 person-years. Included patients fulfilled criteria for the behavioral variant of frontotemporal dementia (BVFTD), the nonfluent variant or semantic variant of primary progressive aphasia (PPA), unspecified PPA, progressive supranuclear palsy, corticobasal syndrome, or frontotemporal dementia with amyotrophic lateral sclerosis (FTD-ALS). Data were analyzed from July 19 to December 7, 2021. MAIN OUTCOMES AND MEASURES: Random-intercept Poisson models were used to obtain estimates of the European FTLD incidence rate accounting for geographic heterogeneity. RESULTS: Based on 267 identified cases (mean [SD] patient age, 66.70 [9.02] years; 156 males [58.43%]), the estimated annual incidence rate for FTLD in Europe was 2.36 cases per 100 000 person-years (95% CI, 1.59-3.51 cases per 100 000 person-years). There was a progressive increase in FTLD incidence across age, reaching its peak at the age of 71 years, with 13.09 cases per 100 000 person-years (95% CI, 8.46-18.93 cases per 100 000 person-years) among men and 7.88 cases per 100 000 person-years (95% CI, 5.39-11.60 cases per 100 000 person-years) among women. Overall, the incidence was higher among men (2.84 cases per 100 000 person-years; 95% CI, 1.88-4.27 cases per 100 000 person-years) than among women (1.91 cases per 100 000 person-years; 95% CI, 1.26-2.91 cases per 100 000 person-years). BVFTD was the most common phenotype (107 cases [40.07%]), followed by PPA (76 [28.46%]) and extrapyramidal phenotypes (69 [25.84%]). FTD-ALS was the rarest phenotype (15 cases [5.62%]). A total of 95 patients with FTLD (35.58%) had a family history of dementia. The estimated number of new FTLD cases per year in Europe was 12 057. CONCLUSIONS AND RELEVANCE: The findings suggest that FTLD-associated syndromes are more common than previously recognized, and diagnosis should be considered at any age. Improved knowledge of FTLD incidence may contribute to appropriate health and social care planning and in the design of future clinical trials.

IMPORTANCE: There is a lack of validated biomarkers for disability progression independent of relapse activity (PIRA) in multiple sclerosis (MS). OBJECTIVE: To determine how serum glial fibrillary acidic protein (sGFAP) and serum neurofilament light chain (sNfL) correlate with features of disease progression vs acute focal inflammation in MS and how they can prognosticate disease progression. DESIGN, SETTING, AND PARTICIPANTS: Data were acquired in the longitudinal Swiss MS cohort (SMSC; a consortium of tertiary referral hospitals) from January 1, 2012, to October 20, 2022. The SMSC is a prospective, multicenter study performed in 8 centers in Switzerland. For this nested study, participants had to meet the following inclusion criteria: cohort 1, patients with MS and either stable or worsening disability and similar baseline Expanded Disability Status Scale scores with no relapses during the entire follow-up; and cohort 2, all SMSC study patients who had initiated and continued B-cell–depleting treatment (ie, ocrelizumab or rituximab). EXPOSURES: Patients received standard immunotherapies or were untreated. MAIN OUTCOMES AND MEASURES: In cohort 1, sGFAP and sNfL levels were measured longitudinally using Simoa assays. Healthy control samples served as the reference. In cohort 2, sGFAP and sNfL levels were determined cross-sectionally. RESULTS: This study included a total of 355 patients (103 [29.0%] in cohort 1: median [IQR] age, 42.1 [33.2-47.6] years; 73 female patients [70.9%]; and 252 [71.0%] in cohort 2: median [IQR] age, 44.3 [33.3-54.7] years; 156 female patients [61.9%]) and 259 healthy controls with a median [IQR] age of 44.3 [36.3-52.3] years and 177 female individuals (68.3%). sGFAP levels in controls increased as a function of age (1.5% per year; P < .001), were inversely correlated with BMI (−1.1% per BMI unit; P = .01), and were 14.9% higher in women than in men (P = .004). In cohort 1, patients with worsening progressive MS showed 50.9% higher sGFAP levels compared with those with stable MS after additional sNfL adjustment, whereas the 25% increase of sNfL disappeared after additional sGFAP adjustment. Higher sGFAP at baseline was associated with accelerated gray matter brain volume loss (per doubling: 0.24% per year; P < .001) but not white matter loss. sGFAP levels remained unchanged during disease exacerbations vs remission phases. In cohort 2, median (IQR) sGFAP z scores were higher in patients developing future confirmed disability worsening compared with those with stable disability (1.94 [0.36-2.23] vs 0.71 [−0.13 to 1.73]; P = .002); this was not significant for sNfL. However, the combined elevation of z scores of both biomarkers resulted in a 4- to 5-fold increased risk of confirmed disability worsening (hazard ratio [HR], 4.09; 95% CI, 2.04-8.18; P < .001) and PIRA (HR, 4.71; 95% CI, 2.05-9.77; P < .001). CONCLUSIONS AND RELEVANCE: Results of this cohort study suggest that sGFAP is a prognostic biomarker for future PIRA and revealed its complementary potential next to sNfL. sGFAP may serve as a useful biomarker for disease progression in MS in individual patient management and drug development.

ObjectivesTo evaluate the combined contribution of brain and cervical cord damage in predicting 5-year clinical worsening in a multicentre cohort of definite multiple sclerosis (MS) patients.MethodsBaseline 3.0T brain and cervical cord T2-weighted and three-dimensional T1-weighted MRI was acquired in 367 patients with MS (326 relapse-onset and 41 progressive-onset) and 179 healthy controls. Expanded Disability Status Scale (EDSS) score was obtained at baseline and after a median follow-up of 5.1 years (IQR=4.8–5.2). At follow-up, patients were classified as clinically stable/worsened according to EDSS changes. Generalised linear mixed models identified predictors of clinical worsening, evolution to secondary progressive (SP) MS and reaching EDSS=3.0, 4.0 and 6.0 milestones at 5 years.ResultsAt follow-up, 120/367 (33%) patients with MS worsened clinically; 36/256 (14%) patients with relapsing–remitting evolved to SPMS. Baseline predictors of EDSS worsening were progressive-onset versus relapse-onset MS (standardised beta (β)=0.97), higher EDSS (β=0.41), higher cord lesion number (β=0.41), lower normalised cortical volume (β=−0.15) and lower cord area (β=−0.28) (C-index=0.81). Older age (β=0.86), higher EDSS (β=1.40) and cord lesion number (β=0.87) independently predicted SPMS conversion (C-index=0.91). Predictors of reaching EDSS=3.0 after 5 years were higher baseline EDSS (β=1.49), cord lesion number (β=1.02) and lower normalised cortical volume (β=−0.56) (C-index=0.88). Baseline age (β=0.30), higher EDSS (β=2.03), higher cord lesion number (β=0.66) and lower cord area (β=−0.41) predicted EDSS=4.0 (C-index=0.92). Finally, higher baseline EDSS (β=1.87) and cord lesion number (β=0.54) predicted EDSS=6.0 (C-index=0.91).ConclusionsSpinal cord damage and, to a lesser extent, cortical volume loss helped predicting worse 5-year clinical outcomes in MS.

•Disease modifying treatments potentially influence response to SARS-CoV-2 mRNA vaccines.•SARS-CoV-2 specific CD4+T cell responses to mRNA vaccines were high in MS patients on ocrelizumab and teriflunomide.•SARS-CoV-2 specific CD4+T cell responses to mRNA vaccines were largely impaired in patients on treatment with S1Pr-mod.•When present, SARS-CoV-2 specific T cells were mainly of Th1 type and stable over time and after booster vaccine doses.

IMPORTANCE: The mechanisms driving neurodegeneration and brain atrophy in relapsing multiple sclerosis (RMS) are not completely understood. OBJECTIVE: To determine whether disability progression independent of relapse activity (PIRA) in patients with RMS is associated with accelerated brain tissue loss. DESIGN, SETTING, AND PARTICIPANTS: In this observational, longitudinal cohort study with median (IQR) follow-up of 3.2 years (2.0-4.9), data were acquired from January 2012 to September 2019 in a consortium of tertiary university and nonuniversity referral hospitals. Patients were included if they had regular clinical follow-up and at least 2 brain magnetic resonance imaging (MRI) scans suitable for volumetric analysis. Data were analyzed between January 2020 and March 2021. EXPOSURES: According to the clinical evolution during the entire observation, patients were classified as those presenting (1) relapse activity only, (2) PIRA episodes only, (3) mixed activity, or (4) clinical stability. MAIN OUTCOMES AND MEASURES: Mean difference in annual percentage change (MD-APC) in brain volume/cortical thickness between groups, calculated after propensity score matching. Brain atrophy rates, and their association with the variables of interest, were explored with linear mixed-effect models. RESULTS: Included were 1904 brain MRI scans from 516 patients with RMS (67.4% female; mean [SD] age, 41.4 [11.1] years; median [IQR] Expanded Disability Status Scale score, 2.0 [1.5-3.0]). Scans with insufficient quality were excluded (n = 19). Radiological inflammatory activity was associated with increased atrophy rates in several brain compartments, while an increased annualized relapse rate was linked to accelerated deep gray matter (GM) volume loss. When compared with clinically stable patients, patients with PIRA had an increased rate of brain volume loss (MD-APC, −0.36; 95% CI, −0.60 to −0.12; P = .02), mainly driven by GM loss in the cerebral cortex. Patients who were relapsing presented increased whole brain atrophy (MD-APC, −0.18; 95% CI, −0.34 to −0.02; P = .04) with respect to clinically stable patients, with accelerated GM loss in both cerebral cortex and deep GM. No differences in brain atrophy rates were measured between patients with PIRA and those presenting relapse activity. CONCLUSIONS AND RELEVANCE: Our study shows that patients with RMS and PIRA exhibit accelerated brain atrophy, especially in the cerebral cortex. These results point to the need to recognize the insidious manifestations of PIRA in clinical practice and to further evaluate treatment strategies for patients with PIRA in clinical trials.

•Prolonged treatment with anti-CD20 antibodies may lead to hypogammaglobulinemia and increased risk of infections in multiple sclerosis.•Cladribine is rarely associated with hypogammaglobulinemia.•After switching from anti-CD20 antibodies to cladribine, serum IgG, IgM, NfL and GFAP concentrations remain stable.•Switching to cladribine is clinically effective as a de-escalation strategy in patients experiencing infections or hypogammaglobulinemia related to anti-CD20 treatment.

We report the analysis of 1 year of data from the first cohort of 15 patients enrolled in an open-label, first-in-human, dose-escalation phase I study (ClinicalTrials.gov: NCT03282760, EudraCT2015-004855-37) to determine the feasibility, safety, and tolerability of the transplantation of allogeneic human neural stem/progenitor cells (hNSCs) for the treatment of secondary progressive multiple sclerosis.

•Accuracy for self-reported disease-modifying therapy (DMT) was high across all tested agents.•Agreement between self-reported and reimbursement-approved DMTs was near-perfect.•Agreement for self-reported MS types ranged from fair to moderate, and accuracy was varying.•Self-reports can serve as suitable surrogates for healthcare provider data in population-based MS research.

ABSTRACTIntroduction:Frontotemporal dementia (FTD) is a heterogeneous clinical entity that includes several disorders characterized by different cellular mechanisms. Distinctive clinical features in FTD include behavioral, affective, and cognitive symptoms. Unfortunately, little progress has been made over the past 20 years in terms of the development of effective disease-modifying drugs with the currently available symptomatic treatments having limited clinical utility.Areas covered:This article reviews the principal pharmacological intervention studies for FTD. These are predominantly randomized clinical trials and include symptomatic treatments and potential disease-modifying drugs.Expert opinion:There is insufficient evidence on effective treatments for FTD and studies with better methodological backgrounds are needed. Most studies reporting therapeutic benefits were conducted with selective serotonin reuptake inhibitors, while anti-dementia drugs have been ineffective in FTD. Since the underlying pathology of FTD mostly consists of abnormal tau protein or TDP-43 aggregates, treatments are being developed to interfere with their aggregation process or with the clearance of these proteins. Furthermore, disease-modifying treatments remain years away as demonstrated by the recent negative Phase III findings of a tau aggregation inhibitor (LMTM) for treating the behavioral variant of FTD. The results from current ongoing Phase I/II trials will hopefully give light to future treatment options.

•Weekly intramuscular IFNB-1a improved injection site tolerability already after 4 months.•Systemic tolerability improved markedly over time.•Good treatment tolerability translated into increased treatment satisfaction after 12 months.•Persistence on treatment with weekly intramuscular IFNB-1a was 77.5% at month 12.

IMPORTANCE: Therapeutic options for patients with secondary progressive multiple sclerosis (SPMS) are limited. OBJECTIVE: To analyze disability progression in patients with SPMS treated with rituximab compared with matched control patients never treated with rituximab. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study analyzed data obtained from patients with SPMS at 3 multiple sclerosis centers located in Basel and Lugano, Switzerland, and Amsterdam, the Netherlands, from 2004 to 2017. Patients were included for analysis if they had received a diagnosis of SPMS, were treated (57 eligible; 54 included) or never treated (504 eligible; 59 included) with rituximab, and had at least 1 follow-up visit. The variables used for propensity score matching were sex, age, Expanded Disability Status Scale (EDSS) score, and disease duration. Follow-up duration was up to 10 years, with a mean (SD) of 3.5 (2.6) years for rituximab-treated patients and 5.4 (2.4) years for controls in the total cohort and a mean (SD) of 3.5 (2.7) years for rituximab-treated patients and 4.8 (2.2) years for controls in the matched cohort. EXPOSURES: Comparing EDSS score progression in patients with SPMS (treated with rituximab vs not treated with rituximab) using propensity score matching. MAIN OUTCOMES AND MEASURES: The primary end point was progression of EDSS score after baseline, and the secondary end point was time to confirmed disability progression. RESULTS: After 1:1 propensity score matching, 44 matched pairs (88 patients) were included in the analysis. At baseline, patients treated with rituximab had a mean (SD) age of 49.7 (10.0) years, mean (SD) disease duration of 18.2 (9.4) years, and mean (SD) EDSS score of 5.9 (1.4), and 26 (59%) were women, whereas controls had a mean (SD) age of 51.3 (7.4) years, mean (SD) disease duration of 19.4 (8.7) years, and mean (SD) EDSS score of 5.70 (1.29), and 27 (61%) were women. In the covariate-adjusted analysis of the matched set, patients with SPMS who were treated with rituximab had a significantly lower EDSS score during a mean (SD) follow-up of 3.5 (2.7) years (mean difference, −0.52; 95% CI, −0.79 to −0.26; P < .001). Time to confirmed disability progression was significantly delayed in the rituximab-treated group (hazard ratio, 0.49; 95% CI, 0.26-0.93; P = .03). CONCLUSIONS AND RELEVANCE: In this study, patients with SPMS treated with rituximab had a significantly lower EDSS score for up to 10 years of follow-up and a significantly delayed confirmed progression compared with matched controls, suggesting that B-cell depletion by rituximab may be therapeutically beneficial in these patients. A prospective randomized clinical trial with a better level of evidence is needed to confirm the efficacy of rituximab in such patients.

•Covid-19 vaccine hesitancy in surveyed persons with MS in Switzerland was very low.•Hesitation to vaccinate was most often a personal preference.•Older age and regular visits to healthcare professionals were negatively associated with hesitancy.•A history of positive Covid-19 test was positively associated with hesitancy.•Covid-19 vaccination usually had mild side effects and rarely affected MS symptoms.

The study by Dubessy et al.1is valuable for its instrumental analysis of sleep, despite the small and cross-sectional design, because it shows a large overlap between sleepiness and fatigue and discloses a subgroup with central-like hypersomnia. We studied 86 patients with MS by polysomnography (PSG) and the maintenance of a wakefulness test (MWT). Dubessy et al. did not identify a consistent group of patients with excessive daytime sleepiness (EDS) and without fatigue. Similarly, only 13% of our sample showed EDS without fatigue. In our sample, fatigue overlapped greater with depression than with EDS. Dubessy et al. excluded depressed patients, exposing their study to a selection bias.

•Almost one third (29.4%) of the survey persons with MS reported volunteering.•Study participants most often volunteered in cultural and charitable organizations.•Having a university degree was positively associated with volunteering.•Being male and being a homemaker increased chances of volunteering.•Having a lower ability to perform everyday tasks decreased chances of volunteering.

•PwMS are 1.5 times more frequently affected by material deprivation than the general Swiss population.•High symptom burden at the transition from work force to receiving disability benefits appeared to be vulnerable for material deprivation.•Higher education, older age, having a Swiss citizenship, living with a spouse or a partner or being currently employed were independently associated with a lower risk of material deprivation.

To elucidate the genetic architecture of amyotrophic lateral sclerosis (ALS) and find associated loci, we assembled a custom imputation reference panel from whole-genome-sequenced patients with ALS and matched controls (n = 1,861). Through imputation and mixed-model association analysis in 12,577 cases and 23,475 controls, combined with 2,579 cases and 2,767 controls in an independent replication cohort, we fine-mapped a new risk locus on chromosome 21 and identified C21orf2 as a gene associated with ALS risk. In addition, we identified MOBP and SCFD1 as new associated risk loci. We established evidence of ALS being a complex genetic trait with a polygenic architecture. Furthermore, we estimated the SNP-based heritability at 8.5%, with a distinct and important role for low-frequency variants (frequency 1–10%). This study motivates the interrogation of larger samples with full genome coverage to identify rare causal variants that underpin ALS risk.

•Associations of age and MS duration with comorbidities and disability were explored using registry data.•Hypertension, diabetes, and cancer were associated with age, and cardiac disease was associated with both age and MS duration.•While having at least moderate gait disability was associated with both age and MS duration, severe was associated with MS duration only.•The spline analysis suggested a non-linear increase of having at least moderate gait disability with age.

Objective:We aimed to investigate the influence of natalizumab (NTZ) treatment on multiple sclerosis course in patients with and without spinal involvement.Methods:Annualized relapse rate (ARR), disability progression and occurrence of new brain and spinal T2 lesions (N2TL) in 68 spinal (S-P) versus 68 non-spinal matched patients (NS-P) were retrospectively collected and compared between before (2 years) and after NTZ treatment using multivariate regression models.Results:Mean duration of NTZ treatment was 31.3 ± 16.3 months in S-P and 32.1 ± 15.1 months in N-SP (p 0.56). The mean ARR after NTZ treatment was similarly reduced in both S-P (0.07 ± 0.19) and N-SP (0.07 ± 0.16) (p < 0.001 for both). Disability progression after NTZ start was similarly low in S-P and NS-P. However, when compared to before NTZ start, disability progression was significantly reduced in S-P (p 0.017), but not in NS-P (p 0.68). This was largely mediated by a higher disability progression before NTZ start in S-P than N-SP. The risk of developing N2TL during NTZ was not different between S-P and NS-P (p 0.10).Conclusions:NTZ similarly reduced the occurrence of relapses and NT2L in S-P and NS-P, whereas the effect on disability progression was particularly evident in the presence of spinal involvement. NTZ appears to be a treatment of high efficacy in both S-P and NS-P.

•Based on 668 relapsing-remitting MS (RRMS) cases, associations of the disease-modifying therapy (DMT) status were explored.•21% of persons were not on a DMT, 67% received a DMT for more, and 13% for less than 6 months.•Disease-modifying therapies (DMTs) reduce relapse rates and disease progression, but not all persons with RRMS receive DMT.•Self-reported side-effects were common and varied substantially across the five most frequently used DMTs.•The majority of persons with RRMS were on long-term DMT, this however does not necessarily imply a burden-free life.

Multiple sclerosis (MS) is a chronic disease of the central nervous system with not yet completely understood pathogenesis. The so called “chronic cerebrospinal venous insufficiency (CCSVI) theory” has recently emerged, supporting the concept of a cerebrospinal venous drainage impairment as the cause of MS. Since the first publication on this topic with a claimed 100% specificity and sensitivity of the condition for MS diagnosis, CCSVI theory has generated a scientific and mass media debate with a great hope for the miracle of a new possible endovascular treatment of MS (“liberation procedure”). We critically summarize the available evidence on CCSVI discussing inconsistent and incomplete replication of the original results by different groups, methodological limitations and potential therapeutic implications. We conclude that the available data are insufficient to establish conclusively a clear relationship between MS and CCSVI and do not support the role of CCSVI as the primary cause of MS. Until credible scientific evidence replicates the original results, any proposed invasive treatments of CCSVI should be discouraged.

•Effectiveness of cladribine appears similar in aged (≥50 years) and young (<50 years) people with MS.•Cladribine-induced lymphopenia is comparable between aged and young people with MS.•Adverse events and infections during cladribine treatment are numerically more frequent among aged and disabled people with MS.

•In MS patients, total sleep time, wake after sleep onset and REM-sleep correlated with cognitive abnormalities.•Worse global cognitive functioning, memory and attention performances were associated with reduced sleep efficacy, and longer periods of nocturnal wake.•Reduced REM-sleep was correlated with poorer attention performances.•Trait anxiety moderated the relationship between nocturnal wake and memory.•Treatment of sleep and psychiatric disturbances may contribute to mitigate cognitive disorders in MS.

Early provision of protein has been shown to limit catabolism and could improve growth. Our objective was to determine whether early aggressive protein intake improved growth outcomes of extremely low birth weight (ELBW) infants.

Early provision of protein has been shown to limit catabolism and could improve growth. Our objective was to determine whether early aggressive protein intake improved growth outcomes of extremely low birth weight (ELBW) infants. ELBW infants were included in the study if they had no major congenital anomalies or renal failure and were still hospitalized at 36 weeks postmenstrual age. In 25 infants (HP) the early protein intake was planned to be 20% greater than in 31 historical controls (SP). The 2 groups were similar in the baseline characteristics. The mean protein intake during the first 14 days of life was significantly greater in the HP group (3.1 ± 0.2 vs 2.5 ± 0.2 g/kg/d; P<0.0001). HP group showed lower postnatal weight loss (−3.1%; 95% confidence interval [CI] −5.9, −0.2) and earlier regain of birth weight (−4.1 days; 95% CI −6.6, −1.7). Mean blood urea nitrogen and bicarbonate levels were similar; mean serum glucose level was lower in the HP group (−21,7 mg/dL; 95% CI −41.9,−1.5). HP infants had a reduced fall in weight zscore (−0.57; 95% CI −1.01, −0.12) and in length zscore (−0.51; 95% CI −0.97, −0.05) from birth to discharge. Early high protein intake was associated with improved weight and length growth outcomes at discharge. These findings highlight the benefits of aggressive protein intake immediately after birth.

We performed a pilot trial investigating the effect of a steroid taper on adrenal function and safety measures after acute MS relapses. Twenty-five patients were randomized to either prednisone taper (n=12) or placebo (n=13) after 3 days of intravenous methylprednisolone. No patient showed signs of adrenal insufficiency at any time by cortisol response to ACTH. This significantly increased between baseline and 6 months in both groups. Patients remained clinically and radiologically stable, but those under prednisone taper experienced more frequently mood disorders, hyperglycaemia and weight increase. If confirmed by sufficiently powered studies, these results would question the need of a steroid taper following short-term intravenous methylprednisolone.

•Physiotherapy (PT) may alleviate multiple sclerosis symptoms, yet little is known about usage and barriers.•PT usage was studied based on self-reports of 1493 Swiss Multiple Sclerosis Registry participants.•PT usage was higher in persons with primary-progressive MS, higher symptom burden, or recent stays at a rehabilitation clinic.•No association between PT supply and percent PT users per Swiss canton was detected.•PT uptake differences were observed by language region, which warrant further investigations.

Clinician-assessed Expanded Disease Status Scale (EDSS) is gold standard in clinical investigations but normally unavailable in population-based, patient-centred MS-studies. Our objective was to develop a self-reported gait measure reflecting EDSS-categories.

•Treatment of a patient with MS rebound after fingolimod withdrawal.•Immune gene profiling showed rapid effects of rituximab on the T cell transcriptome.•Rituximab leads to the normalization of T cell responses even after severe rebound.

Multiple sclerosis (MS) is a mainly demyelinating, autoimmune, and disabling neurological disease. In addition to well-known clinically evident symptoms such as coordination or motor problems, increasing attention has been posed to a constellation of less evident symptoms significantly contributing to the clinical impact of MS. Among others, sleep symptoms have been only recently explored. This systematic review summarizes objective sleep findings detected by using polysomnography and their relationship with clinical variables in MS patients. While it is well known that sleep disorders are frequent in MS, objective clinical data are still scarce. Literature based on subjective reports indicate sleep disorders as highly frequent in MS patients; however, objective data are still scarce. New large case-control instrumental investigations are warranted to establish the real objective entity and impact of sleep comorbidities.